This project is investigating morphologic abnormalities in the skeletal muscle fibers and subterminal motor nerves of schizophrenics, patients with affective psychoses, their first-degree relatives and normal controls. Light phase and electron miscroscopy is utilized. A subtle peripheral neuropathy is present in some patients and their first-degree relatives as indicated by excessive branching of subterminal motor nerves, excessive numbers of scattered atrophic fibers, fiber type grouping and assorted other findings such as Z-band streaming. Abnormalities of the Hoffman-reflex are also present in some patients. The delay in recovery is consistent with increased dopaminergic activitiy in some schizophrenics. Extensive animal studies to explore the relationship between bioamines, brain and muscle disease are also being conducted. Lesions of the ventral pallidum produce muscle degeneration in rats. Serotonin, amine uptake blockers, membrane "labilizers" and monoamine oxidase inhibitors produce skeletal muscle disease. The etiology of this muscle pathology is being studied. The psychotomimetic drug harmaline also produces skeletal muscle pathology in rabbits. The effects of chronic treatment with amine precursors on rate muscle is being studied. BIBLIOGRAPHIC REFERENCES: Meltzer, H.Y.: Skeletal Muscle Necrosis Following Membrane-Active Drugs Plus Serotonin. J. Neurol. Sci. 28:41-56, 1976. Meltzer, H.Y.: Serum Creatine Phosphokinase in Schizophrenia. Amer. J. Psychiatry 133:192-196, 1976.